Regulation of Rad51 function by c-Abl in response to DNA damage.
The Rad51 protein, a homolog of bacterial RecA, functions in DNA double-strand break repair and genetic recombination. Whereas Rad51 catalyzes ATP-dependent pairing and strand exchange between homologous DNA molecules, regulation of this function is unknown. The c-Abl tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. Here we demonstrate that c-Abl interacts constitutively with Rad51. We show that c-Abl phosphorylates Rad51 on Tyr-54 in vitro. The results also show that treatment of cells with ionizing radiation induces c-Abl-dependent phosphorylation of Rad51. Phosphorylation of Rad51 by c-Abl inhibits the binding of Rad51 to DNA and the function of Rad51 in ATP-dependent DNA strand exchange reactions. These findings represent the first demonstration that Rad51 is regulated by phosphorylation and support a functional role for c-Abl in regulating Rad51-dependent recombination in the response to DNA damage.
Yuan
Z M
ZM
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Huang
Y
Y
Ishiko
T
T
Nakada
S
S
Utsugisawa
T
T
Kharbanda
S
S
Wang
R
R
Sung
P
P
Shinohara
A
A
Weichselbaum
R
R
Kufe
D
D
D002460:Cell Line; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D015151:Immunoblotting; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D051135:Rad51 Recombinase; D011839:Radiation, Ionizing; D011995:Recombination, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D019000:Phosphotyrosine; D016315:Proto-Oncogene Proteins c-abl; D051135:Rad51 Recombinase